Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.
Within this definition a particular type of pain associated with neurological abnormalities, called neuropathic pain, is becoming increasingly important due to its significant, growing worldwide prevalence. Neuropathic pain is defined as “pain initiated or caused by a primary lesion or dysfunction in the nervous system”, which may take the form of dysaesthesia, allodynia, hyperpathy, stinging or stabbing pain.
Neuropathic pain is distinguished from other types of commonly reported (nociceptive) pain, including headache, backache, and other types of musculoskeletal pain, and comprises a heterogeneous group of conditions which cannot be explained by a single etiology or a particular anatomical lesion.
These disorders of the structures of the central or peripheral nervous system include various neuropathies (diabetic neuropathy, post-herpetic neuropathy, inflammatory neuropathies, neuropathy caused by alcohol abuse and neuropathy associated with HIV/AIDS infection), and can derive from various toxins (such as neurotoxins), acute trauma (including surgical traumas), chronic trauma (such as repetitive stress syndrome), mononeuropathies, such as carpal tunnel syndrome (the most common type of mononeuropathy, which affects 2.8% to 4.6% of the adult population), and disorders of the central nervous system (such as stroke, multiple sclerosis, cerebral ischaemia, Parkinson's disease, spinal cord lesions and head injuries).
The disorder is not easy to diagnose, because although the nerve produces continual painful discharges, it is often anatomically intact.
Neuropathic pain covers a variety of pathological states and presents with a variety of symptoms, which have the following common denominators:                pain is perceived in the absence of a permanent, identifiable tissue lesion or process;        unpleasant, abnormal or unusual sensations (dysaesthesia) are present, frequently described as stinging or electric shocks;        brief episodes of paroxystic stabbing or piercing pain are present;        the pain appears some time after the lesion that triggered it        the pain is perceived in a region with a sensory deficit;        even mild stimuli are painful (allodynia);        marked summation and persistent activity occur after the application of repeated stimuli.        
It is estimated that neuropathic pain affects up to 3% of the population, and that some 1 to 5% of European adults suffer from chronic pain.
According to the literature, in the USA the problem of neuropathic pain is potentially onerous for the national insurance systems, with a prevalence of 1.5%.                80% of patients with tumours at an advanced stage present neuropathic symptoms.        
Chronic neuropathic pain is a major problem in neurology because it is frequent and often disabling, due to its unpleasant, chronic nature.
It is also a type of pain which does not respond well to the most common analgesics, such as acetylsalicylic acid, paracetamol or the most common non-steroidal anti-inflammatory drugs.
The aim of pharmacological treatments should be to prevent pain, but in practice, the most that can be achieved is to reduce the pain to a bearable level.
At present, no class of drugs has proved universally effective for patients with neuropathic pain.
“Off-label” drugs belonging to the following categories are generally used, but cause serious side effects in the long term:                antidepressants        anticonvulsants (gabapentin)        opioids (methadone, oxycodone)        tramadol        lidocaine        cytokine-inhibiting anti-inflammatories.        
When these drugs are effective, they reduce pain by 25-40% in 40-60% of patients.
Moreover, numerous adverse effects are caused by continuous use of these drugs.
Neuropathic pain therefore represents a major clinical challenge due to its severity, chronic nature, resistance to the usual treatments and serious effect on the quality of the life.
The main research into this disorder uses experimental metabolic, pharmacological or trauma models in rodents, which reproduce the characteristics of human pain symptoms (Ref 1-7).
Hypericum, also known as St. John's Wort, consists of the flowering stems of Hypericum perforatum. It contains a large number of different classes of substances: naphthodianthrone derivatives such as hypericin, pseudohypericin and isohypericin, and phloroglucinol derivatives such as hyperforin. It also contains flavonoids such as hyperoside, rutin, I3,II8-biapigenin, quercetin, quercitrin and isoquercitrin, procyanidins, essential oil and xanthones.
It is widely used in modern phytotherapy to treat some forms of mild or moderate depression and psychovegetative problems, with effective results at the dose of 500-1050 mg of extract/day divided into 2-3 doses, for 2-4 weeks, and fewer side effects than treatment with synthetic antidepressants.
Hypericum perforatum extracts have been tested in many experimental pharmacological and clinical trials, which fully support its use for depression, but many questions about its characteristics still remain unanswered. A number of action mechanisms have been suggested to explain its antidepressant effects: 1) non-selective serotonin, noradrenaline and dopamine reuptake inhibition; 2) increased density of the serotoninergic, dopaminergic and GABA receptors; 3) increased affinity for the GABA receptors; 4) inhibition of the enzyme monoamine oxidase (MAO). The identity of the active components is still in doubt, and its pharmacological activity seems to be complex and determined by the concomitant effects of a number of active substances. Hypericin has been identified as “the” active ingredient, but a new component, hyperforin, which was recently identified, seems to play an important part in the efficacy of the plant, while flavonoids, in particular rutin, have been identified as compounds which can influence its activity (Ref. 8-15).
A clinical trial (16) published in 2000 describes the inefficacy of a hypericum extract in the treatment of neuropathies.
Other studies describe the analgesic activity of hypericum, but they were conducted on different species from Hypericum perforatum, the extracts were not chemically characterised, the administration route was often not oral, and above all, they were evaluated on non-neuropathic pain models (hot plate test, writhing test, Ref. 16-22).